Citation and License

BMC Infectious Diseases 2012, 12:296
doi:10.1186/1471-2334-12-296

Published: 12 November 2012

Abstract

Background

Drug-related toxicity has been one of the main causes of antiretroviral treatment
discontinuation. However, its determinants are not fully understood. Aim of this study
was to investigate predictors of first-line antiretroviral therapy discontinuation
due to adverse events and their evolution in recent years.

Results

1,096 patients were included: 302 discontinuations for adverse events were observed
over 1,861 person years of follow-up between 1988 and 2010, corresponding to an incidence
(95% CI) of 0.16 (0.14-0.18). By Kaplan-Meier estimation, the probabilities (95% CI)
of being free from an adverse event at 90 days, 180 days, one year, two years, and
five years were 0.88 (0.86-0.90), 0.85 (0.83-0.87), 0.79 (0.76-0.81), 0.70 (0.67-0.74),
0.55 (0.50-0.61), respectively. The most represented adverse events were gastrointestinal
symptoms (28.5%), hematological (13.2%) or metabolic (lipid and glucose metabolism,
lipodystrophy) (11.3%) toxicities and hypersensitivity reactions (9.3%). Factors associated
with an increased hazard of adverse events were: older age, CDC stage C, female gender,
homo/bisexual risk group (vs. heterosexual), HBsAg-positivity. Among drugs, zidovudine,
stavudine, zalcitabine, didanosine, full-dose ritonavir, indinavir but also efavirenz
(actually recommended for first-line regimens) were associated to an increased hazard
of toxicity. Moreover, patients infected by HIV genotype F1 showed a trend for a higher
risk of adverse events.

Conclusions

After starting antiretroviral therapy, the probability of remaining free from adverse
events seems to decrease over time. Among drugs associated with increased toxicity,
only one is currently recommended for first-line regimens but with improved drug formulation.
Older age, CDC stage, MSM risk factor and gender are also associated with an increased
hazard of toxicity and should be considered when designing a first-line regimen.